Global and regional burden of stroke during 1990-2010: findings from the Global Burden of Disease Study 2010.
Lancet. 2014 Jan 18;383(9913):245-54
Authors: Feigin VL, Forouzanfar MH, Krishnamurthi R, Mensah GA, Connor M, Bennett DA, Moran AE, Sacco RL, Anderson L, Truelsen T, O'Donnell M, Venketasubramanian N, Barker-Collo S, Lawes CM, Wang W, Shinohara Y, Witt E, Ezzati M, Naghavi M, Murray C, Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) and the GBD Stroke Experts Group
BACKGROUND: Although stroke is the second leading cause of death worldwide, no comprehensive and comparable assessment of incidence, prevalence, mortality, disability, and epidemiological trends has been estimated for most regions. We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) to estimate the global and regional burden of stroke during 1990-2010.
METHODS: We searched Medline, Embase, LILACS, Scopus, PubMed, Science Direct, Global Health Database, the WHO library, and WHO regional databases from 1990 to 2012 to identify relevant studies published between 1990 and 2010.We applied the GBD 2010 analytical technique (DisMod-MR), based on disease-specific, pre-specified associations between incidence, prevalence, and mortality, to calculate regional and country-specific estimates of stroke incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) lost by age group (<75 years, ≥ 75 years, and in total)and country income level (high-income, and low-income and middle-income) for 1990, 2005, and 2010.
FINDINGS: We included 119 studies (58 from high-income countries and 61 from low-income and middle-income countries). From 1990 to 2010, the age-standardised incidence of stroke significantly decreased by 12% (95% CI 6-17)in high-income countries, and increased by 12% (-3 to 22) in low-income and middle-income countries, albeit nonsignificantly. Mortality rates decreased significantly in both high income (37%, 31-41) and low-income and middle income countries (20%, 15-30). In 2010, the absolute numbers of people with fi rst stroke (16・9 million), stroke survivors (33 million), stroke-related deaths (5・9 million), and DALYs lost (102 million) were high and had significantly increased since 1990 (68%, 84%, 26%, and 12% increase, respectively), with most of the burden (68・6% incident strokes, 52・2% prevalent strokes, 70・9% stroke deaths, and 77・7% DALYs lost) in low-income and middle-income countries. In 2010, 5・2 million (31%) strokes were in children (aged <20 years old) and young and middle-aged adults(20-64 years), to which children and young and middle-aged adults from low-income and middle-income countries contributed almost 74 000 (89%) and 4・0 million (78%), respectively, of the burden. Additionally, we noted significant geographical differences of between three and ten times in stroke burden between GBD regions and countries. More than 62% of new strokes, 69・8% of prevalent strokes, 45・5% of deaths from stroke, and 71・7% of DALYs lost because of stroke were in people younger than 75 years.
INTERPRETATION: Although age-standardised rates of stroke mortality have decreased worldwide in the past two decades,the absolute number of people who have a stroke every year, stroke survivors, related deaths, and the overall global burden of stroke (DALYs lost) are great and increasing. Further study is needed to improve understanding of stroke determinants and burden worldwide, and to establish causes of disparities and changes in trends in stroke burden between countries of different income levels.
FUNDING: Bill & Melinda Gates Foundation.
PMID: 24449944 [PubMed - indexed for MEDLINE]
Inpatient rehabilitation centers and concern for increasing volume of ischemic stroke patients requiring rehabilitation.
South Med J. 2013 Dec;106(12):693-6
Authors: Siegler JE, Boehme AK, Fowler BD, George AJ, Monlezun DJ, Albright KC, Beasley TM, Martin-Schild S
OBJECTIVES: To determine whether prolonged length of stay (pLOS) in ischemic stroke is related to delays in discharge disposition arrangement.
METHODS: We designed a retrospective study to compare patients with acute ischemic stroke who experienced pLOS to those who did not experience pLOS. Patients who have had acute ischemic stroke between July 2008 and December 2010 were included unless they arrived >48 hours after time last seen normal, had an unknown last seen normal, or experienced an in-hospital stroke. pLOS was defined in our prospective stroke registry (before the generation of this research question) as hospitalization extended for ≥ 24 hours more than necessary to determine neurologic stability and next level of care/disposition for a given patient. We characterized the frequency of each cause of pLOS and further investigated the destinations that were more frequently associated with pLOS among patients with delay resulting from arranging discharge disposition.
RESULTS: Of the 274 patients included, 106 (31.9%) had pLOS. Reasons for pLOS were discharge disposition (48.1%), non-neurologic medical complications (36.8%), delays in imaging studies (20.8%), awaiting procedure (10.4%), and neurologic complications (9.4%). Among patients with pLOS caused by delayed disposition, more than half were awaiting placement in an inpatient rehabilitation facility.
CONCLUSIONS: For the majority of our patients, pLOS was caused by acquired medical complications and delayed disposition, most commonly inpatient rehabilitation. Further efforts are needed to prevent complications and further investigation is necessary to identify the factors that may contribute to delayed discharge to inpatient rehabilitation facilities, which may include delayed planning or heightened scrutiny of insurance companies regarding their beneficiaries.
PMID: 24305530 [PubMed - indexed for MEDLINE]
Safety profile of high-dose statin therapy in geriatric patients with stroke.
South Med J. 2013 Dec;106(12):658-64
Authors: Manocha D, Bansal N, Gumaste P, Brangman S
OBJECTIVES: Use of high-dose statin therapy (HDST) in patients with stroke became standard clinical practice after the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) study, in which the mean age of the study population was approximately 63 years. Little data are available on the adverse effects of statins when used in high doses in adults older than 65 years. The objective of this study was to assess the magnitude of adverse effects of HDST in geriatric patients.
METHODS: This single-center, retrospective, case-control study was conducted at Upstate Medical University, Syracuse, New York. All patients older than 65 years admitted between 2008 and 2011 to the hospital's Upstate Stroke Center with acute stroke were eligible. Electronic medical records of 200 eligible patients were reviewed to collect demographic, clinical, and laboratory data. Patients on HDST (cases) were compared with those on low doses (controls) using the χ, Fisher exact (two-sided), and Student t tests.
RESULTS: One hundred cases (mean age 80.5 ± 7.7 years) were compared with 100 controls (mean age 78.9 ± 6.4 years). Sixty-seven percent were taking simvastatin. Ninety percent of the cases compared with 81% of the controls had ischemic stroke. The prevalence of elevated alanine aminotransferase (13%) and myositis (4%) was significantly higher in the cases than in the controls. Fourteen percent of the cases reported myalgias, 9% had nausea, and 6% had diarrhea. Seventy-three cases had low-density lipoprotein levels <100 mg% and 41% of the cases had mean glycated hemoglobin levels ≥ 6.5%.
CONCLUSIONS: The use of HDST in older adult patients with acute stroke is associated with a significantly increased burden of liver enzyme elevation and myalgias.
PMID: 24305522 [PubMed - indexed for MEDLINE]
Teaching neuroimages: thalamic aphasia syndrome.
Neurology. 2013 Dec 3;81(23):e177
Authors: Afzal U, Farooq MU
An 83-year-old right-handed woman presented with sudden right-sided hemiparesis, somnolence, and loss of normal speech. Speech was nonfluent with semantic paraphasias and word-finding difficulties. Word repetition and comprehension was normal. MRI brain showed an area of restricted diffusion in the left thalamus consistent with acute infarction (figure 1). Speech fluency returned to normal after 2 days with occasional dysnomia and paraphasias.
PMID: 24297806 [PubMed - indexed for MEDLINE]
Medial medullary infarction with central sparing.
Neurology. 2013 Dec 3;81(23):2054-5
Authors: Ryman DC, Ju YE
A 35-year-old woman had cardiac arrest requiring treatment with a left ventricular assist device. After regaining consciousness, examination revealed upbeating nystagmus, otherwise normal bulbar function, left arm dysmetria, and numbness periorally and in areas she described as "a turtleneck of numbness with a T-shirt of sensation" (figure 1).
PMID: 24297800 [PubMed - indexed for MEDLINE]
Surgical removal of extensive left pulmonary vein stump thrombus after pulmonary lobectomy: a rare cause of acute cerebral embolism.
Ann Thorac Surg. 2013 Dec;96(6):e135-6
Authors: Ohira S, Doi K, Okawa K, Matsushiro T, Yaku H
A 46-year-old woman presented with loss of consciousness and was diagnosed with acute cerebral embolism. She had undergone left upper lobectomy for primary lung cancer 6 months before this event. Transesophageal echocardiography and computed tomography showed a large mobile thrombus in the left upper pulmonary vein (LSPV). An emergent operation was performed through a median sternotomy. Cardiopulmonary bypass was performed and the heart was arrested, and the LSPV was incised. A fresh thrombus had formed in the stump of the LSPV and was removed successfully. The postoperative course was uneventful. During a 1 year of follow-up, there was no recurrence of the thrombus.
PMID: 24296222 [PubMed - indexed for MEDLINE]
Left atrium ball thrombus in a patient with hemorrhagic cerebral infarction.
Ann Thorac Surg. 2013 Dec;96(6):2236-8
Authors: Yasuda S, Tokunaga S, Matsuki Y, Okamoto H, Machida D, Masuda M
The patient was a 72-year-old man with left hemiparesis. Multiple hemorrhagic cerebral infarctions were recognized on a computed tomographic (CT) scan. A transesophageal echocardiogram showed a huge left atrial mass, which was floating and nearly obstructed the mitral orifice in the diastolic phase. Emergency left atrial mass removal was performed. To reduce the risk of critical brain hemorrhage, the dose of heparin was reduced (100 U/kg) and 1 mg/kg/h of nafamostat mesilate was administered into the venous circuit during extracorporeal circulation. A postoperative brain CT scan showed no evidence of deterioration of cerebral hemorrhage. Pathologic examination showed a ball thrombus.
PMID: 24296197 [PubMed - indexed for MEDLINE]
Malignant paraganglioma presenting with hemorrhagic stroke in a child.
Pediatrics. 2013 Dec;132(6):e1709-14
Authors: Luiz HV, da Silva TN, Pereira BD, Santos JG, Gonçalves D, Manita I, Portugal J
Sympathetic paragangliomas are rare catecholamine-secreting tumors of extra-adrenal origin, and their diagnosis in children is even more infrequent. They usually manifest as hypertension, palpitations, headache, sweating, and pallor. Malignant paragangliomas are identified by the presence of metastasis. Hemorrhagic stroke in the pediatric population is a life-threatening condition with several etiologies. We report here the case of a 12-year-old boy with malignant sympathetic paraganglioma presenting with hemorrhagic stroke. Severe hypertension was found and the patient evolved into a coma. Brain computed tomography scan showed right thalamus hemorrhage with intraventricular extension. After clinical improvement, further investigation revealed elevated catecholamine and metanephrine levels, and 2 abdominal tumors were identified by computed tomography. Resection of both lesions was performed, and histologic findings were consistent with paraganglioma. Multiple metastatic involvement of bones and soft tissues appeared several years later. Genetic testing identified a mutation in succinate dehydrogenase subunit B gene, with paternal transmission. 131I-metaiodobenzylguanidine therapy was performed 3 times with no tumoral response. Our patient is alive, with adequate quality of life, 25 years after initial diagnosis. To our knowledge, this is the first pediatric case of paraganglioma presenting with hemorrhagic stroke. Intracerebral hemorrhage was probably caused by severe hypertension due to paraganglioma. Therefore, we expand the recognized clinical spectrum of the disease. Physicians evaluating children with hemorrhagic stroke, particularly if hypertension is a main symptom, should consider the possibility of catecholamine-secreting tumors. Metastatic disease is associated with succinate dehydrogenase subunit B mutations and, although some patients have poor prognosis, progression can be indolent.
PMID: 24276837 [PubMed - indexed for MEDLINE]
Blunt cerebrovascular injury in children: underreported or underrecognized?: A multicenter ATOMAC study.
J Trauma Acute Care Surg. 2013 Dec;75(6):1006-11; discussion 1011-2
Authors: Azarakhsh N, Grimes S, Notrica DM, Raines A, Garcia NM, Tuggle DW, Maxson RT, Alder AC, Recicar J, Garcia-Filion P, Greenwell C, Lawson KA, Wan JY, Eubanks JW
BACKGROUND: Blunt cerebrovascular injury (BCVI) has been well described in the adult trauma literature. The risk factors, proper screening, and treatment options are well known. In pediatric trauma, there has been very little research performed regarding this injury. We hypothesize that the incidence of BCVI in children is lower than the 1% reported incidence in adult studies and that many children at risk are not being screened properly.
METHODS: This is a multi-institutional retrospective cohort study of pediatric patients (<15 years) admitted with blunt trauma to six American College of Surgeons-verified Level 1 pediatric trauma centers between October 2009 and June 2011. All patients with head, neck, or face injuries who were high risk for BCVI based on Memphis criteria were analyzed.
RESULTS: Of 5,829 blunt trauma admissions, 538 patients had at least one of the Memphis criteria. Only 89 (16.5%) of these patients were screened (16 patients had more than one test) by angiography (64 by computed tomography angiography, 39 by magnetic resonance angiography, and 2 by conventional angiography), while 459 (83.5%) were not screened. Screened patients differed from unscreened patients in Injury Severity Score (ISS) (22.6 ± 13.3 vs. 13.3 ± 9.9, p < 0.0001) and head and neck Abbreviated Injury Scale (AIS) score (3.7 ± 1.2 vs. 2.8 ± 1.2, p < 0.0001). The incidence of BCVI in our total population was 0.4% (23 patients). Of the 23 patients with BCVI, 3 (13%) had no risk factors for the injury. The odds of having sustained BCVI in a patient with one or more of the risk factors was 4.0 (95% confidence interval, 1.1-14.2).
CONCLUSION: BCVI in Level 1 pediatric trauma centers is diagnosed less frequently than in adult centers. However, screening was performed in a minority of high-risk patients who may explain the reported lower incidence of BCVI in children. Pediatric surgeons need to become more vigilant about screening pediatric patients with high-risk criteria for BCVI.
LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level III; therapeutic study, level IV.
PMID: 24256674 [PubMed - indexed for MEDLINE]
A prospective evaluation of platelet function in patients on antiplatelet therapy with traumatic intracranial hemorrhage.
J Trauma Acute Care Surg. 2013 Dec;75(6):990-4
Authors: Joseph B, Pandit V, Sadoun M, Larkins CG, Kulvatunyou N, Tang A, Mino M, Friese RS, Rhee P
BACKGROUND: Platelet transfusion is increasingly used in patients with traumatic intracranial hemorrhage (ICH) on aspirin therapy to minimize the progression of ICH. We hypothesized (null) that platelet transfusion in this cohort of patients does not improve platelet function.
METHODS: We performed a prospective interventional trail on patients with traumatic ICH on daily high-dose (325 mg) aspirin therapy. All patients received one pack of apheresis platelets. Blood samples were collected before and 1 hour after platelet transfusion. Platelet function was assessed using Verify Now Platelet Function Assay, and a cutoff of greater than 550 aspirin reaction units was used to define functioning platelets (FP).
RESULTS: Twenty-eight patients were enrolled in the study. On presentation, 79% (22 of 28) of the patients had nonfunctioning platelets (NFPs), and transfusion of platelets did not improve platelet function as 81% (18 of 22) still had NFP. Of the 22 patients, 4 converted from NFP to FP after transfusion. There was no difference in the progression of ICH (37.5% vs. 30%, p = 0.7) or neurosurgical intervention (12.5% vs. 15%, p = 0.86) between patients with FP and NFP after platelet transfusion.
CONCLUSION: Administration of one pack of apheresis platelet did not improve platelet function. In our study, progression of ICH and the need for neurosurgical intervention were independent of platelet function. Further randomized clinical trials are required to assess both the dose dependence effect and role of platelet transfusion in patients on antiplatelet therapy with traumatic ICH.
LEVEL OF EVIDENCE: Therapeutic study, level III.
PMID: 24256671 [PubMed - indexed for MEDLINE]
The effects of body weight support treadmill training with power-assisted functional electrical stimulation on functional movement and gait in stroke patients.
Am J Phys Med Rehabil. 2013 Dec;92(12):1051-9
Authors: Lee HJ, Cho KH, Lee WH
OBJECTIVE: The aim of the current study was to examine the effect of body weight support treadmill training (BWSTT) with power-assisted functional electrical stimulation on functional movement and gait in stroke patients.
DESIGN: Thirty stroke patients were randomly assigned to either the experimental group (n = 15) or the control group (n = 15). All subjects participated in the same standard rehabilitation program. In addition, the experimental group participated in BWSTT with power-assisted functional electrical stimulation for 30 mins per day, five times a week, for 4 wks, and those in the control group participated in BWSTT for 30 minutes per day, five times a week, for 4 wks. Functional movement was assessed using the Berg Balance Scale, the Timed Up and Go test, and the Stroke Rehabilitation Assessment of Movement. Gait ability was assessed using an electrical walkway system.
RESULTS: Significant differences in the time factor for functional movement and gait (P < 0.05) were observed in the experimental and control groups. For the group × time interaction, significant improvements were observed in the functional movement (Berg Balance Scale [10.93 vs. 6.00], Timed Up and Go test [-9.25 vs. -5.25 secs], and Stroke Rehabilitation Assessment of Movement scores [14.07 vs. 9.80]) and gait (velocity [40.07 vs. 18.64 cm/sec], cadence [30.57 vs. 17.75 steps per minute], paretic side step length [19.36 vs. 8.46 cm], and stride length [30.57 vs. 12.71 cm]) (P < 0.05).
CONCLUSIONS: The findings of the current study demonstrated the efficacy of BWSTT with power-assisted functional electrical stimulation on the functional movement and gait ability in stroke patients. Therefore, the authors suggest that power-assisted functional electrical stimulation may be an effective method for the improvement of functional movement and gait ability of stroke patients when added to BWSTT.
PMID: 24252934 [PubMed - indexed for MEDLINE]
Edoxaban versus warfarin in patients with atrial fibrillation.
N Engl J Med. 2013 Nov 28;369(22):2093-104
Authors: Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, Waldo AL, Ezekowitz MD, Weitz JI, Špinar J, Ruzyllo W, Ruda M, Koretsune Y, Betcher J, Shi M, Grip LT, Patel SP, Patel I, Hanyok JJ, Mercuri M, Antman EM, ENGAGE AF-TIMI 48 Investigators
BACKGROUND: Edoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects. The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known.
METHODS: We conducted a randomized, double-blind, double-dummy trial comparing two once-daily regimens of edoxaban with warfarin in 21,105 patients with moderate-to-high-risk atrial fibrillation (median follow-up, 2.8 years). The primary efficacy end point was stroke or systemic embolism. Each edoxaban regimen was tested for noninferiority to warfarin during the treatment period. The principal safety end point was major bleeding.
RESULTS: The annualized rate of the primary end point during treatment was 1.50% with warfarin (median time in the therapeutic range, 68.4%), as compared with 1.18% with high-dose edoxaban (hazard ratio, 0.79; 97.5% confidence interval [CI], 0.63 to 0.99; P<0.001 for noninferiority) and 1.61% with low-dose edoxaban (hazard ratio, 1.07; 97.5% CI, 0.87 to 1.31; P=0.005 for noninferiority). In the intention-to-treat analysis, there was a trend favoring high-dose edoxaban versus warfarin (hazard ratio, 0.87; 97.5% CI, 0.73 to 1.04; P=0.08) and an unfavorable trend with low-dose edoxaban versus warfarin (hazard ratio, 1.13; 97.5% CI, 0.96 to 1.34; P=0.10). The annualized rate of major bleeding was 3.43% with warfarin versus 2.75% with high-dose edoxaban (hazard ratio, 0.80; 95% CI, 0.71 to 0.91; P<0.001) and 1.61% with low-dose edoxaban (hazard ratio, 0.47; 95% CI, 0.41 to 0.55; P<0.001). The corresponding annualized rates of death from cardiovascular causes were 3.17% versus 2.74% (hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), and 2.71% (hazard ratio, 0.85; 95% CI, 0.76 to 0.96; P=0.008), and the corresponding rates of the key secondary end point (a composite of stroke, systemic embolism, or death from cardiovascular causes) were 4.43% versus 3.85% (hazard ratio, 0.87; 95% CI, 0.78 to 0.96; P=0.005), and 4.23% (hazard ratio, 0.95; 95% CI, 0.86 to 1.05; P=0.32).
CONCLUSIONS: Both once-daily regimens of edoxaban were noninferior to warfarin with respect to the prevention of stroke or systemic embolism and were associated with significantly lower rates of bleeding and death from cardiovascular causes. (Funded by Daiichi Sankyo Pharma Development; ENGAGE AF-TIMI 48 ClinicalTrials.gov number, NCT00781391.).
PMID: 24251359 [PubMed - indexed for MEDLINE]
Outcomes following transcatheter aortic valve replacement in the United States.
JAMA. 2013 Nov 20;310(19):2069-77
Authors: Mack MJ, Brennan JM, Brindis R, Carroll J, Edwards F, Grover F, Shahian D, Tuzcu EM, Peterson ED, Rumsfeld JS, Hewitt K, Shewan C, Michaels J, Christensen B, Christian A, O'Brien S, Holmes D, STS/ACC TVT Registry
IMPORTANCE: Transcatheter aortic valve replacement (TAVR) was approved by the US Food and Drug Administration for the treatment of severe, symptomatic aortic stenosis and inoperable status (in 2011) and high-risk but operable status (starting in 2012). A national registry (the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy [STS/ACC TVT] Registry) was initiated to meet a condition for Medicare coverage and also facilitates outcome assessment and comparison with other trials and international registries.
OBJECTIVE: To report the initial US commercial experience with TAVR.
DESIGN, SETTING, AND PARTICIPANTS: We obtained results from all eligible US TAVR cases (n=7710) from 224 participating registry hospitals following the Edwards Sapien XT device commercialization (November 2011-May 2013).
MAIN OUTCOMES AND MEASURES: Primary outcomes included all-cause in-hospital mortality and stroke following TAVR. Secondary analyses included procedural complications and outcomes by clinical indication and access site. Device implantation success was defined as successful vascular access, deployment of a single device in the proper anatomic position, appropriate valve function without either moderate or severe AR, and successful retrieval of the delivery system. Thirty-day outcomes are presented for a representative 3133 cases (40.6%) at 114 centers with at least 80% complete follow-up reporting.
RESULTS: The 7710 patients who underwent TAVR included 1559 (20%) cases that were inoperable and 6151 (80%) cases that were high-risk but operable. The median age was 84 years (interquartile range [IQR], 78-88 years); 3783 patients (49%) were women and the median STS predicted risk of mortality was 7% (IQR, 5%-11%). At baseline, 2176 patients (75%) were either not at all satisfied (1297 patients [45%]) or mostly dissatisfied (879 patients [30%]) with their symptom status; 2198 (72%) had a 5-m walk time longer than 6 seconds (slow gait speed). The most common vascular access approach was transfemoral (4972 patients [64%]), followed by transapical (2197 patients [29%]) and other alternative approaches (536 patients [7%]); successful device implantation occurred in 7069 patients (92%; 95% CI, 91%-92%). The observed incidence of in-hospital mortality was 5.5% (95% CI, 5.0%-6.1%). Other major complications included stroke (2.0%; 95% CI, 1.7%-2.4%), dialysis-dependent renal failure (1.9%; 95% CI, 1.6%-2.2%), and major vascular injury (6.4%; 95% CI, 5.8%-6.9%). Median hospital stay was 6 days (IQR, 4-10 days), with 4613 (63%) discharged home. Among patients with available follow-up at 30 days (n=3133), the incidence of mortality was 7.6% (95% CI, 6.7%-8.6%) (noncardiovascular cause, 52%); a stroke had occurred in 2.8% (95% CI, 2.3%-3.5%), new dialysis in 2.5% (95% CI, 2.0%-3.1%), and reintervention in 0.5% (95% CI, 0.3%-0.8%).
CONCLUSIONS AND RELEVANCE: Among patients undergoing TAVR at US centers in the STS/ACC TVT Registry, device implantation success was achieved in 92% of cases, the overall in-hospital mortality rate was 5.5%, and the stroke rate was 2.0%. Although these postmarket US approval findings are comparable with prior published trial data and international experience, long-term follow-up is essential to assess continued efficacy and safety.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01737528.
PMID: 24240934 [PubMed - indexed for MEDLINE]
Spice, pot, and stroke.
Neurology. 2013 Dec 10;81(24):2064-5
Authors: Brust JC
The endocannabinoid system includes 2 types of G-protein coupled receptors: CB1 (mostly in the brain) and CB2 (in peripheral lymphoid tissue). The major cannabinoid ligands are arachidonylethanolamine ("anandamide," the Sanskrit word for bliss) and 2-arachidonylglycerol ("2AG"). It is by binding to CB1 receptors that δ-9-tetrahydrocannabinol (THC), the principal psychoactive ingredient in marijuana ("pot"), produces its intended subjective effects.
PMID: 24212392 [PubMed - indexed for MEDLINE]
Long-term predictive value of the Framingham Risk Score for Stroke in HIV-positive vs HIV-negative men.
Neurology. 2013 Dec 10;81(24):2094-102
Authors: Mateen FJ, Post WS, Sacktor N, Abraham AG, Becker JT, Smith BR, Detels R, Martin E, Phair JP, Shinohara RT, Multicenter AIDS Cohort Study (MACS) Investigators
OBJECTIVE: To test the predictive accuracy of the Framingham Risk Score for Stroke (FRS-S) in HIV-infected (HIV+) vs HIV-uninfected (HIV-) men.
METHODS: The Multicenter AIDS Cohort Study (MACS) is an ongoing prospective study of HIV+ and HIV- men who have sex with men (MSM) enrolled in 4 US cities. We ascertained all reported stroke events during a recent 15-year timeframe (July 1, 1996 to June 30, 2011) among 3,945 participants (1,776 HIV+ and 2,169 HIV-). For those with strokes, FRS-S were calculated 10 years before the stroke event and assessed according to HIV status.
RESULTS: A total of 114 stroke events occurred, including 57 HIV+ and 37 HIV- participants with first-ever strokes and 19 fatal strokes. The incidence of first-ever stroke was 1.7/1,000 person-years among HIV- and 3.3/1,000 person-years among HIV+ participants. Among those with strokes, HIV+ participants were younger than HIV- participants (median age 51.3 vs 61.8 years, p < 0.0001). For these men with stroke, the average 10-year risk of stroke was higher for HIV- MSM (6.6% [range 3%-26%] vs 4.9% for HIV+ MSM [range 0%-15%], p < 0.04). Traditional risk factors for stroke were similar among the Framingham cohort and the MACS HIV+ and HIV- participants.
CONCLUSIONS: FRS-S prediction was systematically different in HIV+ vs HIV- men with stroke events. The FRS-S underestimates the long-term risk of stroke in HIV+ men.
PMID: 24212385 [PubMed - indexed for MEDLINE]
Ischemic stroke after use of the synthetic marijuana "spice".
Neurology. 2013 Dec 10;81(24):2090-3
Authors: Freeman MJ, Rose DZ, Myers MA, Gooch CL, Bozeman AC, Burgin WS
OBJECTIVES: To report and associate acute cerebral infarctions in 2 young, previously healthy siblings with use of the street drug known as "spice" (a synthetic marijuana product, also known as "K2"), which they independently smoked before experiencing acute embolic-appearing ischemic strokes.
METHODS: We present history, physical examination, laboratory data, cerebrovascular imaging, echocardiogram, ECG, and hospital course of these patients.
RESULTS: We found that in both siblings spice was obtained from the same source. The drug was found to contain the schedule I synthetic cannabinoid JWH-018. Full stroke workup was unrevealing of a stroke etiology; urine drug screen was positive for marijuana.
CONCLUSIONS: We found that our 2 patients who smoked the street drug spice had a temporal association with symptoms of acute cerebral infarction. This association may be confounded by contaminants in the product consumed (i.e., marijuana or an unidentified toxin) or by an unknown genetic mechanism. The imaging of both patients suggests an embolic etiology, which is consistent with reports of serious adverse cardiac events with spice use, including tachyarrhythmias and myocardial infarctions.
PMID: 24212384 [PubMed - indexed for MEDLINE]
Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels.
JAMA. 2013 Nov 6;310(17):1829-36
Authors: Vigen R, O'Donnell CI, Barón AE, Grunwald GK, Maddox TM, Bradley SM, Barqawi A, Woning G, Wierman ME, Plomondon ME, Rumsfeld JS, Ho PM
IMPORTANCE: Rates of testosterone therapy are increasing and the effects of testosterone therapy on cardiovascular outcomes and mortality are unknown. A recent randomized clinical trial of testosterone therapy in men with a high prevalence of cardiovascular diseases was stopped prematurely due to adverse cardiovascular events raising concerns about testosterone therapy safety.
OBJECTIVES: To assess the association between testosterone therapy and all-cause mortality, myocardial infarction (MI), or stroke among male veterans and to determine whether this association is modified by underlying coronary artery disease.
DESIGN, SETTING, AND PATIENTS: A retrospective national cohort study of men with low testosterone levels (<300 ng/dL) who underwent coronary angiography in the Veterans Affairs (VA) system between 2005 and 2011.
MAIN OUTCOMES AND MEASURES: Primary outcome was a composite of all-cause mortality, MI, and ischemic stroke.
RESULTS: Of the 8709 men with a total testosterone level lower than 300 ng/dL, 1223 patients started testosterone therapy after a median of 531 days following coronary angiography. Of the 1710 outcome events, 748 men died, 443 had MIs, and 519 had strokes. Of 7486 patients not receiving testosterone therapy, 681 died, 420 had MIs, and 486 had strokes. Among 1223 patients receiving testosterone therapy, 67 died, 23 had MIs, and 33 had strokes. The absolute rate of events were 19.9% in the no testosterone therapy group vs 25.7% in the testosterone therapy group, with an absolute risk difference of 5.8% (95% CI, -1.4% to 13.1%) at 3 years after coronary angiography. In Cox proportional hazards models adjusting for the presence of coronary artery disease, testosterone therapy use as a time-varying covariate was associated with increased risk of adverse outcomes (hazard ratio, 1.29; 95% CI, 1.04 to 1.58). There was no significant difference in the effect size of testosterone therapy among those with and without coronary artery disease (test for interaction, P = .41).
CONCLUSIONS AND RELEVANCE: Among a cohort of men in the VA health care system who underwent coronary angiography and had a low serum testosterone level, the use of testosterone therapy was associated with increased risk of adverse outcomes. These findings may inform the discussion about the potential risks of testosterone therapy.
PMID: 24193080 [PubMed - indexed for MEDLINE]
B-type natriuretic peptides and mortality after stroke: a systematic review and meta-analysis.
Neurology. 2013 Dec 3;81(23):1976-85
Authors: García-Berrocoso T, Giralt D, Bustamante A, Etgen T, Jensen JK, Sharma JC, Shibazaki K, Saritas A, Chen X, Whiteley WN, Montaner J
OBJECTIVE: To measure the association of B-type natriuretic peptide (BNP) and N-terminal fragment of BNP (NT-proBNP) with all-cause mortality after stroke, and to evaluate the additional predictive value of BNP/NT-proBNP over clinical information.
METHODS: Suitable studies for meta-analysis were found by searching MEDLINE and EMBASE databases until October 26, 2012. Weighted mean differences measured effect size; meta-regression and publication bias were assessed. Individual participant data were used to estimate effects by logistic regression and to evaluate BNP/NT-proBNP additional predictive value by area under the receiver operating characteristic curves, and integrated discrimination improvement and categorical net reclassification improvement indexes.
RESULTS: Literature-based meta-analysis included 3,498 stroke patients from 16 studies and revealed that BNP/NT-proBNP levels were 255.78 pg/mL (95% confidence interval [CI] 105.10-406.47, p = 0.001) higher in patients who died; publication bias entailed the loss of this association. Individual participant data analysis comprised 2,258 stroke patients. After normalization of the data, patients in the highest quartile had double the risk of death after adjustment for clinical variables (NIH Stroke Scale score, age, sex) (odds ratio 2.30, 95% CI 1.32-4.01 for BNP; and odds ratio 2.63, 95% CI 1.75-3.94 for NT-proBNP). Only NT-proBNP showed a slight added value to clinical prognostic variables, increasing discrimination by 0.028 points (integrated discrimination improvement index; p < 0.001) and reclassifying 8.1% of patients into correct risk mortality categories (net reclassification improvement index; p = 0.003). Neither etiology nor time from onset to death affected the association of BNP/NT-proBNP with mortality.
CONCLUSION: BNPs are associated with poststroke mortality independent of NIH Stroke Scale score, age, and sex. However, their translation to clinical practice seems difficult because BNP/NT-proBNP add only minor predictive value to clinical information.
PMID: 24186915 [PubMed - indexed for MEDLINE]
Predicting stroke mortality: BNP could it be?
Neurology. 2013 Dec 3;81(23):1970-1
Authors: Jickling GC, Foerch C
Physicians, patients, and families rely on clinical factors associated with stroke mortality to guide decisions of care and set goals of medical therapy. However, these factors, including age and baseline neurologic impairment, are at best imperfect predictors and additional prognostic tools are needed. Biomarkers such as B-type natriuretic peptide (BNP) have potential. However, for a biomarker to be of clinical utility, it needs to add information beyond what clinical predictors can provide. BNP is produced by myocardial tissue in response to strain and acts to reduce systolic blood pressure through vasodilation and natriuresis. In stroke, BNP has been associated with increased mortality.
PMID: 24186914 [PubMed - indexed for MEDLINE]
Comment: Natriuretic peptides as predictive biomarkers of stroke outcome.
Neurology. 2013 Dec 3;81(23):1983
Authors: Coull BM
B-type natriuretic peptide (BNP), along with an inactive N-terminal peptide fragment (NT-proBNP), is secreted by cardiac ventricular myocytes in response to excessive myocardial stretching. The plasma half-life of these peptides is 0.3 and 2.0 hours, respectively, so a single measurement mostly reflects recent cardiac stress that may for example reflect sympathetic stimulation in response to acute stroke. Results from a variety of clinical studies indicate that these peptides may be useful as biomarkers for a variety of both cardiac and cerebrovascular events. In a carefully performed meta-analysis, García-Berrocoso and colleagues(1) evaluate the relationship of BNP and NT-proBNP levels with mortality following acute stroke. Although individuals in the highest quartile for either of the 2 peptides had twice the risk of death compared to the lower quartiles, only the NT-proBNP measures added slightly (additional 8.1% of patients) to the typical clinical measures for predicting stroke mortality including age, sex, and NIH Stroke Scale score. The results do not go far enough to establish a relationship between the cause of death and the highest natriuretic levels. Some suggestive data from the ARISTOTLE trial indicate that cardiac death has an important role but more careful studies that focus on the usefulness of measuring BNP or NT-proBNP within the first 24 hours after acute stroke, along with an analysis of the explicit causes of death, are needed.(2.)
PMID: 24186913 [PubMed - indexed for MEDLINE]